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Copyright of Folia Pharmaceutica Cassoviensia is the property of University of Veterinary Medicine & Pharmacy in Kosice and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and objectives: Post-pubertal disappearance of menstrual cycles (secondary amenorrhea) associated with premature follicular depletion is a heterogeneous condition. Patients with this disease have low levels of gonadal hormones and high levels of gonadotropins. It is one of the causes of female infertility and a strong genetic component is attributed as an underlying cause of this condition. Although variants in several genes have been associated with the condition, the cause of the disease remains undetermined in the vast majority of cases. Methodology and Materials: Ten Saudi married women experiencing secondary amenorrhea were referred to a center for genetics and inherited diseases for molecular investigation. A family-based study design was used. Intensive clinical examinations, including pelvic ultra-sonography (U/S) and biochemical evaluations, were carried out. Karyotypes were normal in all cases and polycystic ovarian syndrome (PCOS) was excluded by using Rotterdam consensus criteria. Patients' DNA samples were whole-exome sequenced (WES). Bidirectional Sanger sequencing was then utilized to validate the identified candidate variants. The pathogenicity of detected variants was predicted using several types of bioinformatics software. Results: Most of the patients have a normal uterus with poor ovarian reserves. Exome sequence data analysis identified candidate variants in genes associated with POI in 60% of cases. Novel variants were identified in HS6ST1, MEIOB, GDF9, and BNC1 in POI-associated genes. Moreover, a homozygous variant was also identified in the MMRN1 gene. Interestingly, mutations in MMRN1 have never been associated with any human disease. The variants identified in this study were not present in 125 healthy Saudi individuals. Conclusions: WES is a powerful tool to identify the underlying variants in genetically heterogeneous diseases like secondary amenorrhea and POI. In this study, we identified six novel variants and expanded the genotype continuum of POI. Unravelling the genetic landscape of POI will help in genetic counselling, management, and early intervention. [ABSTRACT FROM AUTHOR]

Background: DICER1, a cancer predisposition syndrome (CPS), seems to escape timely diagnosis in pediatric patients. Case report 1: A 16-year-old female patient was referred to the endocrinology ward due to a large goiter. Her medical history indicated normal sexual maturation, with menarche occurring at 13.5 years. Over the past 2.5 years, she had developed pronounced androgenic symptoms, including a deepened male voice; facial, back, and neckline acne; hirsutism; and menstrual irregularities leading to secondary amenorrhea. A thyroid ultrasound identified a multinodular goiter (MNG) with cystic–solid lesions containing calcifications. An abdominal ultrasound identified a 5.7 × 6.9 cm solid mass in the right adnexal region, displacing the uterus to the left. Histopathological examination confirmed a Sertoli–Leydig cell tumor. The patient was subjected to a total thyroidectomy. Histopathology revealed benign follicular cell-derived neoplasms. Thyroid follicular nodular disease (TFND) was diagnosed bilaterally. DNA analysis using NGS, confirmed via the Sanger method, revealed a pathogenic heterozygotic variant c.2953C>T [p.Gln985*] in exon 18 of the DICER1 gene. Case report 2: A 12-year-old male patient was admitted to the pediatric surgery unit due to a 33 mL goiter. A month prior to his admission, the patient discovered a palpable nodule in his neck, accompanied by hoarseness. An ultrasound revealed MNG. Molecular analysis revealed a pathogenic heterozygotic variant c.2782C>T [p.Gln928*] in exon 17 of the DICER1 gene. Subsequently, a total thyroidectomy was performed, and histopathological examination revealed TFND bilaterally. Conclusions: Recent advances in genetic evaluation and in histological approaches indicate that MNG/TFND, although rare in the pediatric population, when accompanied by characteristic ultrasound and histopathological features, and by additional features such as androgenization, may warrant assessment also of the DICER1 gene within CPS molecular panel screening. [ABSTRACT FROM AUTHOR]

Copyright of Romanian Journal of Family Medicine / Revista Română de Medicina Familiei is the property of Media DOM Express and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Menstruation is an important physiological function of the female reproductive system. The absence of menstruation is called amenorrhea. Many genetic and nongenetic causes are responsible for primary or secondary amenorrhea. This study aimed to determine the types chromosomal abnormalities among patients with primary or secondary amenorrhea. Methods: It was a cross-sectional study conducted in the Department of Pathology, Bangabandhu Sheikh Mujib Medical University, Dhaka, from September 2019 to August 2021. A total of 115 women who had come for a karyotype test with complaints of pathological amenorrhea were purposively selected. One hundred five cases presented with primary amenorrhea, and 10 cases presented with secondary amenorrhea. Karyotype analysis in peripheral blood by G-banding was carried out using the standard method. Results: Among the 105 patients with primary amenorrhea, 53.3% of patients had a normal karyotype (46, XX), and 46.6% had chromosomal abnormalities (numerical or structural). Turner syndrome classic, 45, XO (16.2%) and 46, XY DSD (Disorders of Sexual Development) (11.4%) were the two most frequent chromosomal abnormalities found in the patients with primary amenorrhea. Among the 10 cases with secondary amenorrhea, seven patients had normal karyotype, and three patients had chromosomal abnormalities (2 had sex chromosomal abnormalities, and 1 had a structural abnormality of autosome). Conclusion: The study of chromosomal abnormalities will help in the early and accurate diagnosis of the underlying aetiology of primary or secondary amenorrhea. It will also help in the management and proper counselling of cases.

Background and objectives: Post-pubertal disappearance of menstrual cycles (secondary amenorrhea) associated with premature follicular depletion is a heterogeneous condition. Patients with this disease have low levels of gonadal hormones and high levels of gonadotropins. It is one of the causes of female infertility and a strong genetic component is attributed as an underlying cause of this condition. Although variants in several genes have been associated with the condition, the cause of the disease remains undetermined in the vast majority of cases. Methodology and Materials: Ten Saudi married women experiencing secondary amenorrhea were referred to a center for genetics and inherited diseases for molecular investigation. A family-based study design was used. Intensive clinical examinations, including pelvic ultra-sonography (U/S) and biochemical evaluations, were carried out. Karyotypes were normal in all cases and polycystic ovarian syndrome (PCOS) was excluded by using Rotterdam consensus criteria. Patients’ DNA samples were whole-exome sequenced (WES). Bidirectional Sanger sequencing was then utilized to validate the identified candidate variants. The pathogenicity of detected variants was predicted using several types of bioinformatics software. Results: Most of the patients have a normal uterus with poor ovarian reserves. Exome sequence data analysis identified candidate variants in genes associated with POI in 60% of cases. Novel variants were identified in HS6ST1, MEIOB, GDF9, and BNC1 in POI-associated genes. Moreover, a homozygous variant was also identified in the MMRN1 gene. Interestingly, mutations in MMRN1 have never been associated with any human disease. The variants identified in this study were not present in 125 healthy Saudi individuals. Conclusions: WES is a powerful tool to identify the underlying variants in genetically heterogeneous diseases like secondary amenorrhea and POI. In this study, we identified six novel variants and expanded the genotype continuum of POI. Unravelling the genetic landscape of POI will help in genetic counselling, management, and early intervention.

Background: DICER1, a cancer predisposition syndrome (CPS), seems to escape timely diagnosis in pediatric patients. Case report 1: A 16-year-old female patient was referred to the endocrinology ward due to a large goiter. Her medical history indicated normal sexual maturation, with menarche occurring at 13.5 years. Over the past 2.5 years, she had developed pronounced androgenic symptoms, including a deepened male voice; facial, back, and neckline acne; hirsutism; and menstrual irregularities leading to secondary amenorrhea. A thyroid ultrasound identified a multinodular goiter (MNG) with cystic–solid lesions containing calcifications. An abdominal ultrasound identified a 5.7 × 6.9 cm solid mass in the right adnexal region, displacing the uterus to the left. Histopathological examination confirmed a Sertoli–Leydig cell tumor. The patient was subjected to a total thyroidectomy. Histopathology revealed benign follicular cell-derived neoplasms. Thyroid follicular nodular disease (TFND) was diagnosed bilaterally. DNA analysis using NGS, confirmed via the Sanger method, revealed a pathogenic heterozygotic variant c.2953C>T [p.Gln985*] in exon 18 of the DICER1 gene. Case report 2: A 12-year-old male patient was admitted to the pediatric surgery unit due to a 33 mL goiter. A month prior to his admission, the patient discovered a palpable nodule in his neck, accompanied by hoarseness. An ultrasound revealed MNG. Molecular analysis revealed a pathogenic heterozygotic variant c.2782C>T [p.Gln928*] in exon 17 of the DICER1 gene. Subsequently, a total thyroidectomy was performed, and histopathological examination revealed TFND bilaterally. Conclusions: Recent advances in genetic evaluation and in histological approaches indicate that MNG/TFND, although rare in the pediatric population, when accompanied by characteristic ultrasound and histopathological features, and by additional features such as androgenization, may warrant assessment also of the DICER1 gene within CPS molecular panel screening.

Secondary amenorrhea is the absence of menses for more than 3 months in women who previously had regular menstrual cycles or 6 months for those with irregular cycles. Workup of secondary amenorrhea includes laboratory analysis to assess pituitary function, specifically luteinizing hormone (LH) and follicle stimulating hormone (FSH). If low, structural evaluation of the pituitary gland with MRI is recommended. We report a case of a 31-year-old female with history of transfusion-dependent Diamond-Blackfan anemia and type 2 diabetes that reported amenorrhea for 1 year following intrauterine device (IUD) removal. Due to low LH and FSH, the patient underwent an MRI of the pituitary gland. Imaging demonstrated complete absence of MRI signal within the pituitary parenchyma, which confirmed pituitary dysfunction from secondary hemochromatosis, presumably due to iron overload from multiple transfusions. As a result of her imaging and laboratory assessment, she was placed on an iron chelator and oral contraception., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)